G protein-coupled receptors (GPCR) are seven-transmembrane receptors and serve to transduce the signals of hormones, neurotransmitters, cytokines or other molecules to the inside of cell membranes. GPR30 is one of GPCR and its ligand is not reported. In regard to human GPR30 (hGPR30) (BBRC, 228, 285-292, 1996), the following reports are found.
When human umbilical vein endothelial cells were exposed to shear stress, the expression level of hGPR30 increased (BBRC, 240, 734-741, 1997). The expression level of rat GPR30 (rGPR30, also known as GPR41) in cardiomyocytes is induced by returning to normal incubation after stimulation under hypoxic conditions (J. Biol. Chem., 276, 26453-26460, 2001). hGPR30 is expressed in breast cancer tissues, breast cancer-derived cell lines and placenta expressing the estrogen receptor (ER) (Genomics, 45, 607-617, 1997). By progestin stimulation in MCF7 breast cancer cells in the presence of estrogen, the expression level of GPR30 increased (Endocrinology, 143 (9), 3376-3384, 2002). Sex hormones are known to regulate many reproductive functions. For example, progesterone inhibits estrogen-induced growth of endometrial endothelial cells in the uterus. On the other hand, most of the functions of progesterone on mammary gland have not been understood yet. Progestin inhibits the growth of breast cancer cells and normal mammary epithelial cells. Progestin-induced growth inhibition of MCF7 cells was triggered by an increased level of GPR30 expression and such was demonstrated by experiments with antisense RNA, implying that GPR30 might be involved in the growth inhibition of breast cancer cell lines (Endocrinology, 143 (9), 3376-3384, 2002).
It is reported that 4-hydroxyphenylretinamide (4-HPR) is an agonist for nuclear receptor PAR and induces apoptosis of various cancer cells (The Journal of Biological Chemistry, 271 (37), 22441-22446, 1996).